ANTI B4 BLOCKED RICIN PLUS IFN ALPHA IN RELAPSED REFRACTORYTOPATHOLOGY

免疫毒素抗-B4/封闭蓖麻毒素在I期安全给药 审判到pts。复发性/难治性B细胞淋巴瘤，中度 抗肿瘤活性的证据。 该协议试图开发一个 增加活动量的方案。 FCRDC的Fogler和Pearson博士 证实，IFN-α与2种 免疫毒素，这两个识别抗原存在于目标 细胞 此外，在体内，非细胞毒性浓度的IFN-α 增强的免疫毒素诱导的肿瘤细胞蛋白质合成抑制 是由一种尚未确定的机制造成的 随后的体内研究表明， 使用抗B4 bR作为抗淋巴瘤细胞的免疫毒素得到类似的结果 线与IFN-α组合。 本研究的目的是：1） 评估IFN-α的临床毒性并确定其MTD， 门诊治疗方案中的抗B4 bR; 2）观察任何抗肿瘤反应 其与组合一起发生，以及，3）表征宿主免疫 对抗B4 bR和IFN-α的组合的反应。 重量份接收 抗B4 bR，从30 mcg/kg（瘦体重）/d开始连续输注 通过7天给药，7天停药方案，随后剂量递增至35 mcg/kg/d。 IFN-α通过每日SQ注射以20 mg/kg的剂量施用。 0.75-6.0万单位/m2/d。 重量份复发/耐药NHL患者 合资格的.治疗28天后，pts.在可接受的毒性下， 抗肿瘤活性的证据，且未产生宿主抗体 有反应的人有资格再治疗。 我们计划增加24个百分点。本 study. 到目前为止，11分。已经得到了治疗。 所有患者均接受30 mcg/kg/d 抗B4/bR抗体 六个，四个是惰性淋巴瘤，两个是大细胞 淋巴瘤--接受了0.75 mu/m2的IFN，5例接受了1.5 mu/m2。 未观察到抗肿瘤反应。

The immunotoxin anti-B4/blocked ricin was administered safely in Phase I trials to pts. with relapsed/refractory B-cell lymphoma, with modest evidence of antitumor activity. This protocol attempts to develop a regimen with increased activity. Drs. Fogler and Pearson of FCRDC demonstrated, in vivo synergy between IFN-alpha and each of 2 immunotoxins, both of which recognized antigens present in the target cells. Also, in vivo, IFN-alpha in non-cytotoxic concentrations potentiated immunotoxin-induced inhibition of tumor cell protein synthesis by an as yet undetermined mechanism. Subsequent in vivo work demonstrated similar results using anti-B4bR as the immunotoxin against lymphoma cell lines in combination with IFN-alpha. The objectives of this study are: 1) to evaluate the clinical toxicity and determine the MTD of IFN-alpha and anti-B4bR in an outpatient regimen; 2) to observe any antitumor responses which occur with the combination and, 3) to characterize the host immune response to the combination of anti-B4bR and IFN-alpha. Pts. receive anti-B4bR beginning at 30 mcg/kg (lean body mass)/d by continuous infusion by a 7-day on, 7-day off schedule, with subsequent dose escalation to 35 mcg/kg/d. IFN-alpha is administered by daily SQ injection, at doses of 0.75-6.0 million units/m2/d. Pts. with relapsed/resistant NHL are eligible. After 28 days treatment, pts. with acceptable toxicity, some evidence of antitumor activity, and no development of a host antibody response are eligible for retreatment. We plan to accrue 24 pts. to this study. So far, 11 pts. have been treated. All have received 30 mcg/kg/d of anti-B4/bR. Six--four with indolent lymphomas and 2 with large cell lymphomas--have received IFN at 0.75 mu/m2, and 5 have received 1.5 mu/m2. No antitumor responses have been observed.